392 research outputs found

    Creating a Culture of Thinking that Cultivates the Perspective-Taking Disposition

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    Through action research, the researchers engaged a group of third grade children in a project that offered a variety of learning activities to develop the children’s perspective-taking ability. As a result the teachers found a significant increase in the emotional connection of the students to the characters in the literature

    Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction

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    Immune mechanisms have been implicated in placental dysfunction in patients with recurrent miscarriages and intrauterine growth restriction (IUGR), but the mediators are undefined. Here we show that complement activation, particularly C5a, is a required intermediary event in the pathogenesis of placental and fetal injury in an antibody-independent mouse model of spontaneous miscarriage and IUGR, and that complement activation causes dysregulation of the angiogenic factors required for normal placental development. Pregnancies complicated by miscarriage or growth restriction were characterized by inflammatory infiltrates in placentas, functional deficiency of free vascular endothelial growth factor (VEGF), elevated levels of soluble VEGF receptor 1 (sVEGFR-1, also known as sFlt-1; a potent anti-angiogenic molecule), and defective placental development. Inhibition of complement activation in vivo blocked the increase in sVEGFR-1 and rescued pregnancies. In vitro stimulation of monocytes with products of the complement cascade directly triggered release of sVEGFR-1, which sequesters VEGF. These studies provide the first evidence linking the complement system to angiogenic factor imbalance associated with placental dysfunction, and identify a new effector of immune-triggered pregnancy complications

    Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study

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    Objectives The interleukin-6 receptor (IL-6R) blocker tocilizumab (TCZ) reduces inflammatory disease activity in rheumatoid arthritis (RA) but elevates lipid concentrations in some patients. We aimed to characterise the impact of IL-6R inhibition on established and novel risk factors in active RA. Methods Randomised, multicentre, two-part, phase III trial (24-week double-blind, 80-week open-label), MEASURE, evaluated lipid and lipoprotein levels, high-density lipoprotein (HDL) particle composition, markers of coagulation, thrombosis and vascular function by pulse wave velocity (PWV) in 132 patients with RA who received TCZ or placebo. Results Median total-cholesterol, low-density lipoprotein-cholesterol (LDL-C) and triglyceride levels increased in TCZ versus placebo recipients by week 12 (12.6% vs 1.7%, 28.1% vs 2.2%, 10.6% vs −1.9%, respectively; all p&#60;0.01). There were no significant differences in mean small LDL, mean oxidised LDL or total HDL-C concentrations. However, HDL-associated serum amyloid A content decreased in TCZ recipients. TCZ also induced reductions (&#60;30%) in secretory phospholipase A2-IIA, lipoprotein(a), fibrinogen and D-dimers and elevation of paraoxonase (all p&#60;0.0001 vs placebo). The ApoB/ApoA1 ratio remained stable over time in both groups. PWV decreases were greater with placebo than TCZ at 12 weeks (adjusted mean difference 0.79 m/s (95% CI 0.22 to 1.35; p=0.0067)). Conclusions These data provide the first detailed evidence for the modulation of lipoprotein particles and other surrogates of vascular risk with IL-6R inhibition. When compared with placebo, TCZ induced elevations in LDL-C but altered HDL particles towards an anti-inflammatory composition and favourably modified most, but not all, measured vascular risk surrogates. The net effect of such changes for cardiovascular risk requires determination.</p

    Net benefits of smallholder dairy cattle farms in Senegal can be significantly increased through the use of better dairy cattle breeds and improved management practices

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    Senegal, located in West Africa, is an example of a low-to middle-income country where the govern-ment has prioritized improving livestock production self-sufficiency, with a strong focus on dairy. Among other initiatives, the use of exotic dairy cattle has been promoted, despite no evidence for the potential liveli-hood benefits (or otherwise) to smallholder farmers on adopting the new genetics. The current work fills this evidence gap by performing a farm-level economic study comparing the keeping of different breed and cross-breed types of dairy cattle under different management levels. Data for the study were obtained by monitoring 220 smallholder dairy cattle farms, with a combined cattle population of about 3,000 animals, over an almost 2-yr period. Findings of the study suggest that the most net-beneficial and cost-beneficial dairy cattle enterprise that could be used by the smallholder farmers was to keep crossbred indigenous zebu by exotic Bos taurus animals under management standards that are consid-ered good compared with local standards. This dairy enterprise type was 7.4-fold more net beneficial and had a 1.4-fold more favorable cost-benefit ratio than the traditional system of keeping indigenous zebu animals under poor (low-input) management. Interestingly, the keeping of (near) pure B. taurus dairy cattle resulted in the highest milk yields and thus benefit from milk, but was not the most net beneficial due to the high costs of keeping these animals, particularly in terms of feed. We also found that increasing the managementlevel of any of the breed or cross-breed types under consideration, including the indigenous zebu animals, resulted in an increased net benefit of 2.2-to 2.9-fold. Results of this economic analysis are discussed as part of a broader trade-off analysis, resulting in recommendations to strengthen the Senegal dairy sector. The combined intervention of improved dairy cattle genetics and management is considered a promising intervention to improve livelihoods of the rural poor as well as livestock production self-sufficiency for Senegal; some other system constraints are addressed.Peer reviewe

    A Novel Polymorphism of FcgammaRIIIa (CD16) Alters Receptor Function and Predisposes to Autoimmune Disease

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    A novel polymorphism in the extracellular domain 2 (EC2) of FcgammaRIIIA affects ligand binding by natural killer (NK) cells and monocytes from genotyped homozygous normal donors independently of receptor expression. The nonconservative T to G substitution at nucleotide 559 predicts a change of phenylalanine (F) to valine (V) at amino acid position 176. Compared with F/F homozygotes, FcgammaRIIIa expressed on NK cells and monocytes in V/V homozygotes bound more IgG1 and IgG3 despite identical levels of receptor expression. In response to a standard aggregated human IgG stimulus, FcgammaRIIIa engagement on NK cells from V/V (high-binding) homozygotes led to a larger rise in [Ca2+]i, a greater level of NK cell activation, and a more rapid induction of activation-induced cell death (by apoptosis). Investigation of an independently phenotyped normal cohort revealed that all donors with a low binding phenotype are F/F homozygotes, while all phenotypic high binding donors have at least one V allele. Initial analysis of 200 patients with SLE indicates a strong association of the low binding phenotype with disease, especially in patients with nephritis who have an underrepresentation of the homozygous high binding phenotype. Thus, the FcgammaRIIIa polymorphism at residue 176 appears to impact directly on human biology, an effect which may extend beyond autoimmune disease characterized by immune complexes to host defense mechanisms

    Evaluation of Food for Life 2013-15: Summary and synthesis report

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    This is the final report of the phase two evaluation of Food for Life undertaken by the University of the West of England, Bristol 2013-15. The research encompassed five workstreams: 1.Long term impacts and durability - understanding how and why the Food for Life approach is embedded in schools for the medium to long-term. 2.Review of local commissions - understanding strategic support for Food for Life, and recommending monitoring and evaluation systems.3.Cross sectional study of pupils’ diets in Food for Life local commissions - evaluating Food for Life’s impact on healthy eating behaviours in schools in local commission areas. 4.New settings - exploring innovative approaches to extending the Food for Life whole setting approach beyond schools.5.Social value of Food for Life in local authority commissions – understanding the social, health, economic and environmental value of Food for Life commissions. The report presents summaries of the findings of each workstream, discusses themes emerging across the research, and sets out recommendations for Food for Life and associated evaluation activity

    Mutations in Complement Regulatory Proteins Predispose to Preeclampsia: A Genetic Analysis of the PROMISSE Cohort

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    Jane Salmon and colleagues studied 250 pregnant patients with SLE and/or antiphospholipid antibodies and found an association of risk variants in complement regulatory proteins in patients who developed preeclampsia, as well as in preeclampsia patients lacking autoimmune disease
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